Since the principle odor constituents of natural musks are macrocyclic compounds, numerous synthetic methods have been devised for the preparation of various macrocycles in an attempt to duplicate the natural musk odor. The method most commonly used for the preparation of lactones, ether-lactones and cyclic esters is the depolymerization of the corresponding linear polyester accompanied by ring closure. For example, lactones are obtained by depolymerizing the high molecular weight product obtained from the condensation of hydroxy acids, e.g. 15-hydroxypentadecanoic acid. Similarly, macrocyclic esters result when polyesters obtained by the condensation of dicarboxylic acids and diols are depolymerized.
Depolymerization procedures are described in U.S. Pat. No. 2,092,031, Czech Pat. No. 108,762 and the article by E. W. Spanagel and W. H. Carothers in J. Amer. Chem. Soc., Vol. 57, 929-934 (1935). In a typical process of this type, the polyester is heated at an elevated temperature, but below the temperature of thermal decomposition, in the presence of an inorganic catalyst. The catalyst is generally a chloride, nitrate, carbonate, borate, oxide, hydroxide or organic acid salt of a divalent metal such as magnesium, manganese, iron, cobalt, lead or tin. The depolymerization is carried out under reduced pressure and the macrocyclic compound and other volatile products formed during the course of the reaction removed from the reaction vessel.
While depolymerization procedures are presently considered to be the best and therefore preferred method for synthesizing macrocyclic lactones, ether-lactones and esters, such processes are not without certain disadvantages. The principle difficulty with depolymerization processes of this type is the viscosity of the reaction mass. The linear polyesters are themselves highly viscous materials by virtue of their high molecular weight but during the depolymerization reaction the viscosity is even further increased so that an intractable plastic mass is formed due to chain-growth reactions occuring between partially depolymerized fragments present in the reaction mass. It is not uncommon, even during the very early stages of depolymerization, for the reaction mass to become so viscous that agitation by conventional means is not possible. Heat transfer within such highly viscous, virtually solid reaction masses is very poor resulting in a highly inefficient reaction, namely, a slow rate of depolymerization and the formation of large amounts of undesirable by-products.
As a result of the viscosity/heat transfer problems associated with these reactions, long reaction times are required even when using the most effective catalysts and reduced pressure and it is not feasible to carry out these reactions on a large scale and obtain acceptable yields of the desired macrocyclic compounds. Accordingly, it has not heretofore been possible to carry out these depolymerizations as anything but batch-type operations, thereby severely limiting the practical utility of such processes for commercial purposes. Even with batch-type operations it has been necessary to conduct the reaction on a relatively small scale and unless very elaborate process equipment designed to maximize heat transfer is used, it is possible to operate at only a fraction of the total reactor capacity to avoid destructive thermal decomposition, excessive foaming and other related problems. It would be highly advantageous therefore, if depolymerization processes could be conducted on a larger scale while minimizing the viscosity/heat transfer problems. It would be even more desirable if the depolymerization could be conducted as a continuous or semi-continuous operation and if high yields of the macrocyclic compounds were possible.